This invention relates to novel pyrazole derivatives and the synthetic intermediates thereof, which have excellent pharmacological actions.
In more detail, this invention relates to the compounds represented by the general formula: ##STR2## wherein R is an alkyl group and D is an alkoxy group, a hydroxyl group, a halogen atom, or an amino group which may be substituted, and the salts thereof, which have powerful antagonistic actions to angiotensin II and hypotensive actions, and thus are useful as therapeutics for diseases of the cardiovascular system, such as hypertension, heart disease, and cerebral stroke.
The renin-angiotensin system is involved in the homeostasis to control systemic blood pressure, body fluid amount, and balance among the electrolytes, together with the aldosterone system. The relation between the renin-angiotensin system and hypertension has been clarified based on the fact that an inhibitor of an angiotensin converting enzyme (ACE inhibitor) which produces angiotensin II having potent vasoconstrictive action has been developed. Because angiotensin II elevates blood pressure via the angiotensin II receptors on the cellular membrane, the antagonist of angiotensin II, like an ACE inhibitor can be used for the treatment of hypertension. Many angiotensin II-related substances, such as saralasin and [Sar.sup.1, Ala.sup.8 ] AII, have been reported to have potent angiotensin II antagonism. However, peptide antagonists have been reported to have short duration of the action after parenteral administration and to be ineffective after oral administration [M. A. Ondetti and D. W. Cushman, Annual Reports in Medicinal Chemistry, 13, 82-91 (1978)].
Non-peptide angiotensin II antagonists include imidazole derivatives having angiotensin II antagonism disclosed in Japanese Unexamined Patent Publication Nos. 71073/1981, 71074/1981, 92270/1982, 157768/1983, 23868/1988, and 117876/1989, A. T. Chiu et al., Eur. J. Pharm., 157, 13 (1988), P. C. Wong et al., J. Pharmacol. Exp. Ther., 247, 1 (1988), and P. C. Wong et al., Hypertension, 13, 489 (1989), and pyrazole derivatives having angiotensin II antagonism reported in European Unexamined Patent Publication No. 0323841.
However, the compounds represented by the formula (I) wherein R is an alkyl group and D is an alkoxy group, a hydroxyl group, a halogen atom, or an amino group which may be substituted have not been disclosed in the literature.